The role of the macrophage in the afferent arm of the immune response of mice to endogenous, ecotropic murine leukemia virus (MuLV) will be examined. Several lines of evidence indicate that the MuLV-specific immune response may be an important host defense in the regulation of virus proliferation and hence as a host defense against malignancy. The macrophage plays a key role in the initiation of many immune responses. Its function, however, in the immune response to MuLV has not been characterized. This macrophage function will be defined by exposing purified macrophage populations to MuLV or MuLV antigens in vitro and subsequently assessing their ability to initiate a specific immune response in several different systems. These experiments will include an in vitro T-cell proliferation assay, an in vitro assay for MuLV-specific T-helper cell activity, and in vivo adoptive transfer techniques. The examination of macrophage function will be applied to two experimental systems which the principal investigator has previously developed. The first is a model for studying the influence of the major histocompatibility complex (MHC, H-2) upon susceptibility to virus infection. There is evidence that this influence may reflect the operation of an immune response (Ir) gene, possibly expressed through the macrophage. The second system involves the phenomenon of neonatal susceptibility of mice to MuLV infection, which may be due to a lack of functionally mature macrophages.